Pretreatment circulating MAIT cells, neutrophils, and periostin predicted the real-world response after 1-year mepolizumab treatment in asthmatics
Background: Mepolizumab treatment improves symptom control and quality of life and reduces exacerbations in patients with severe eosinophilic asthma. However, biomarkers that predict therapeutic effectiveness must be determined for use in precision medicine. Herein, we elucidated the dynamics of var...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Allergology International |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1323893023000503 |
| _version_ | 1797365576703672320 |
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| author | Hitoshi Sasano Norihiro Harada Sonoko Harada Tomohito Takeshige Yuuki Sandhu Yuki Tanabe Ayako Ishimori Kei Matsuno Tetsutaro Nagaoka Jun Ito Asako Chiba Hisaya Akiba Ryo Atsuta Kenji Izuhara Sachiko Miyake Kazuhisa Takahashi |
| author_facet | Hitoshi Sasano Norihiro Harada Sonoko Harada Tomohito Takeshige Yuuki Sandhu Yuki Tanabe Ayako Ishimori Kei Matsuno Tetsutaro Nagaoka Jun Ito Asako Chiba Hisaya Akiba Ryo Atsuta Kenji Izuhara Sachiko Miyake Kazuhisa Takahashi |
| author_sort | Hitoshi Sasano |
| collection | DOAJ |
| description | Background: Mepolizumab treatment improves symptom control and quality of life and reduces exacerbations in patients with severe eosinophilic asthma. However, biomarkers that predict therapeutic effectiveness must be determined for use in precision medicine. Herein, we elucidated the dynamics of various parameters before and after treatment as well as patient characteristics predictive of clinical responsiveness to mepolizumab after 1-year treatment. Methods: Twenty-seven patients with severe asthma were treated with mepolizumab for one year. Asthma control test scores, pulmonary function tests, fractional exhaled nitric oxide levels, and blood samples were evaluated. Additionally, we explored the role of CD69-positive mucosal-associated invariant T (MAIT) cells as a candidate biomarker for predicting treatment effectiveness by evaluating an OVA-induced asthma murine model using MR1 knockout mice, where MAIT cells were absent. Results: The frequencies of CD69-positive group 1 innate lymphoid cells, group 3 innate lymphoid cells, natural killer cells, and MAIT cells decreased after mepolizumab treatment. The frequency of CD69-positive MAIT cells and neutrophils was lower and serum periostin levels were higher in responders than in non-responders. In the OVA-induced asthma murine model, CD69-positive MAIT cell count in the whole mouse lung was significantly higher than that in the control mice. Moreover, OVA-induced eosinophilic airway inflammation was exacerbated in the MAIT cell-deficient MR1 knockout mice. Conclusions: This study shows that circulating CD69-positive MAIT cells, neutrophils, and serum periostin might predict the real-world response after 1-year mepolizumab treatment. Furthermore, MAIT cells potentially have a protective role against type 2 airway inflammation. |
| first_indexed | 2024-03-08T16:51:54Z |
| format | Article |
| id | doaj.art-5758b03e97514f70b482392b1bb3d7df |
| institution | Directory Open Access Journal |
| issn | 1323-8930 |
| language | English |
| last_indexed | 2024-03-08T16:51:54Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Allergology International |
| spelling | doaj.art-5758b03e97514f70b482392b1bb3d7df2024-01-05T04:23:36ZengElsevierAllergology International1323-89302024-01-0173194106Pretreatment circulating MAIT cells, neutrophils, and periostin predicted the real-world response after 1-year mepolizumab treatment in asthmaticsHitoshi Sasano0Norihiro Harada1Sonoko Harada2Tomohito Takeshige3Yuuki Sandhu4Yuki Tanabe5Ayako Ishimori6Kei Matsuno7Tetsutaro Nagaoka8Jun Ito9Asako Chiba10Hisaya Akiba11Ryo Atsuta12Kenji Izuhara13Sachiko Miyake14Kazuhisa Takahashi15Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, JapanDepartment of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan; Research Institute for Diseases of Old Ages, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan; Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan; Corresponding author. Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, 3-1-3 Hongo, Bunkyo-ku, Tokyo 113-8431, Japan.Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan; Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo, JapanDepartment of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, JapanDepartment of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, JapanDepartment of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, JapanDepartment of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, JapanDepartment of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, JapanDepartment of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, JapanDepartment of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, JapanDepartment of Immunology, Juntendo University Graduate School of Medicine, Tokyo, JapanDepartment of Immunology, Juntendo University Graduate School of Medicine, Tokyo, JapanDepartment of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, JapanDivision of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga, JapanDepartment of Immunology, Juntendo University Graduate School of Medicine, Tokyo, JapanDepartment of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan; Research Institute for Diseases of Old Ages, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, JapanBackground: Mepolizumab treatment improves symptom control and quality of life and reduces exacerbations in patients with severe eosinophilic asthma. However, biomarkers that predict therapeutic effectiveness must be determined for use in precision medicine. Herein, we elucidated the dynamics of various parameters before and after treatment as well as patient characteristics predictive of clinical responsiveness to mepolizumab after 1-year treatment. Methods: Twenty-seven patients with severe asthma were treated with mepolizumab for one year. Asthma control test scores, pulmonary function tests, fractional exhaled nitric oxide levels, and blood samples were evaluated. Additionally, we explored the role of CD69-positive mucosal-associated invariant T (MAIT) cells as a candidate biomarker for predicting treatment effectiveness by evaluating an OVA-induced asthma murine model using MR1 knockout mice, where MAIT cells were absent. Results: The frequencies of CD69-positive group 1 innate lymphoid cells, group 3 innate lymphoid cells, natural killer cells, and MAIT cells decreased after mepolizumab treatment. The frequency of CD69-positive MAIT cells and neutrophils was lower and serum periostin levels were higher in responders than in non-responders. In the OVA-induced asthma murine model, CD69-positive MAIT cell count in the whole mouse lung was significantly higher than that in the control mice. Moreover, OVA-induced eosinophilic airway inflammation was exacerbated in the MAIT cell-deficient MR1 knockout mice. Conclusions: This study shows that circulating CD69-positive MAIT cells, neutrophils, and serum periostin might predict the real-world response after 1-year mepolizumab treatment. Furthermore, MAIT cells potentially have a protective role against type 2 airway inflammation.http://www.sciencedirect.com/science/article/pii/S1323893023000503AsthmaMepolizumabMucosal-associated invariant T cellsPeriostinType 2 airway inflammation |
| spellingShingle | Hitoshi Sasano Norihiro Harada Sonoko Harada Tomohito Takeshige Yuuki Sandhu Yuki Tanabe Ayako Ishimori Kei Matsuno Tetsutaro Nagaoka Jun Ito Asako Chiba Hisaya Akiba Ryo Atsuta Kenji Izuhara Sachiko Miyake Kazuhisa Takahashi Pretreatment circulating MAIT cells, neutrophils, and periostin predicted the real-world response after 1-year mepolizumab treatment in asthmatics Allergology International Asthma Mepolizumab Mucosal-associated invariant T cells Periostin Type 2 airway inflammation |
| title | Pretreatment circulating MAIT cells, neutrophils, and periostin predicted the real-world response after 1-year mepolizumab treatment in asthmatics |
| title_full | Pretreatment circulating MAIT cells, neutrophils, and periostin predicted the real-world response after 1-year mepolizumab treatment in asthmatics |
| title_fullStr | Pretreatment circulating MAIT cells, neutrophils, and periostin predicted the real-world response after 1-year mepolizumab treatment in asthmatics |
| title_full_unstemmed | Pretreatment circulating MAIT cells, neutrophils, and periostin predicted the real-world response after 1-year mepolizumab treatment in asthmatics |
| title_short | Pretreatment circulating MAIT cells, neutrophils, and periostin predicted the real-world response after 1-year mepolizumab treatment in asthmatics |
| title_sort | pretreatment circulating mait cells neutrophils and periostin predicted the real world response after 1 year mepolizumab treatment in asthmatics |
| topic | Asthma Mepolizumab Mucosal-associated invariant T cells Periostin Type 2 airway inflammation |
| url | http://www.sciencedirect.com/science/article/pii/S1323893023000503 |
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